Use of mesenchymal stromal cell exosomes in antenatal therapy

Abstract

Provided herein are methods of using mesenchymal stem cell (MSC) exosomes to treat placental insufficiency and/or infertility in a female subject, and/or treating fetal growth restriction in a fetus.

What is claimed is: 
     
         1 . A method of treating placental insufficiency in a female subject, the method comprising administering to the subject an effective amount of a mesenchymal stem cell (MSC) exosome. 
     
     
         2 . The method of  claim 1 , wherein the isolated MSC exosome is isolated from MSC-conditioned media. 
     
     
         3 . The method of  claim 1  or  claim 2 , wherein the MSC is from Warton's Jelly or bone marrow. 
     
     
         4 . The method of any one of  claims 1 - 3 , wherein the female subject is a human subject. 
     
     
         5 . The method of any one of  claims 1 - 4 , wherein the female subject has preeclampsia. 
     
     
         6 . The method of any one of  claims 1 - 5 , wherein the female subject has intrauterine inflammation. 
     
     
         7 . The method of any one of  claims 1 - 6 , wherein the female subject has infertility. 
     
     
         8 . The method of any one of  claims 1 - 7 , wherein the placental insufficiency results in fetal growth restriction and/or fetal loss. 
     
     
         9 . The method of any one of  claims 1 - 8 , wherein the MSC exosome is administered once. 
     
     
         10 . The method of any one of  claims 1 - 8 , wherein the MSC exosome is administered repeatedly. 
     
     
         11 . The method of any one of  claims 1 - 10 , wherein the MSC exosome is administered via intravenous injection. 
     
     
         12 . The method of any one of  claims 1 - 10 , wherein the MSC exosome is administered via intrauterine injection. 
     
     
         13 . The method of any one of  claims 1 - 12 , wherein the MSC exosome is administered antepartum. 
     
     
         14 . The method of any one of  claims 1 - 12 , wherein the MSC exosome is administered intrapartum. 
     
     
         15 . The method of any one of  claims 1 - 14 , wherein the MSC exosome reduces intrauterine inflammation. 
     
     
         16 . The method of any one of  claims 1 - 15 , wherein the MSC exosome reverses placental insufficiency. 
     
     
         17 . The method of any one of  claims 1 - 16 , wherein the MSC exosome reduces the likelihood of fetal growth restriction and/or fetal loss. 
     
     
         18 . Use of a mesenchymal stem cell (MSC) exosome to treat placental insufficiency in a female subject. 
     
     
         19 . A method of treating fetal growth restriction, the method comprising administering to a fetus in a pregnant female subject an effective amount of a mesenchymal stem cell (MSC) exosome. 
     
     
         20 . The method of  claim 19 , wherein the isolated MSC exosome is isolated from MSC-conditioned media. 
     
     
         21 . The method of  claim 19  or  claim 20 , wherein the MSC is from Warton's Jelly or bone marrow. 
     
     
         22 . The method of any one of  claims 19 - 21 , wherein the fetus is a human fetus. 
     
     
         23 . The method of any one of  claims 19 - 22 , wherein the fetal growth restriction is caused by placental insufficiency of the pregnant female subject. 
     
     
         24 . The method of any one of  claims 19 - 23 , wherein the MSC exosome is administered via intravenous injection to the pregnant female subject. 
     
     
         25 . The method of any one of  claims 19 - 23 , wherein the MSC exosome is administered to the amniotic fluid of the pregnant female subject. 
     
     
         26 . The method of any one of  claims 19 - 23 , wherein the MSC exosome is administered via injection into the umbilical vein of the umbilical cord. 
     
     
         27 . The method of any one of  claims 19 - 25 , wherein the MSC exosome is administered once. 
     
     
         28 . The method of any one of  claims 19 - 25 , wherein the MSC exosome is administered repeatedly. 
     
     
         29 . The method of any one of  claims 19 - 28 , wherein the MSC exosome is administered antenatal. 
     
     
         30 . The method of any one of  claims 19 - 28 , wherein the MSC exosome is administered intrapartum. 
     
     
         31 . The method of any one of  claims 19 - 28 , wherein the MSC exosome is administered perinatal. 
     
     
         32 . The method of any one of  claims 19 - 31 , wherein the MSC exosome reduces the likelihood of fetal loss. 
     
     
         33 . The method of any one of  claims 19 - 31 , wherein the MSC exosome ameliorates pre-eclampsia-related alterations in fetal lung development. 
     
     
         34 . Use of a mesenchymal stem cell (MSC) exosome to treat fetal growth restriction of a fetus in a pregnant female subject. 
     
     
         35 . A method of treating infertility, the method comprising administering to a female subject in need thereof an effective amount of a mesenchymal stem cell (MSC) exosome. 
     
     
         36 . The method of  claim 35 , wherein the isolated MSC exosome is isolated from MSC-conditioned media. 
     
     
         37 . The method of  claim 35  or  claim 36 , wherein the MSC is from Warton's Jelly or bone marrow. 
     
     
         38 . The method of any one of  claims 35 - 37 , wherein the subject is a human subject. 
     
     
         39 . The method of any one of  claims 35 - 38 , wherein the female subject has history of pelvic inflammatory disease, advanced maternal age, obesity, metabolic or cardiovascular disease, history of endometriosis or fibroids, chronic maternal hypertension, polycystic ovary syndrome, and/or history of sexually transmitted infections with secondary scarring. 
     
     
         40 . The method of any one of  claims 35 - 39 , wherein the subject has intrauterine inflammation. 
     
     
         41 . The method of any one of  claims 35 - 40 , wherein the subject has placental insufficiency. 
     
     
         42 . The method of any one of  claims 35 - 41 , wherein the MSC exosome is administered once. 
     
     
         43 . The method of any one of  claims 35 - 41 , wherein the MSC exosome is administered repeatedly. 
     
     
         44 . The method of any one of  claims 35 - 43 , wherein the MSC exosome is administered via intravenous injection. 
     
     
         45 . The method of any one of  claims 35 - 43 , wherein the MSC exosome is administered via intrauterine injection. 
     
     
         46 . Use of a mesenchymal stem cell (MSC) exosome to treat infertility in a female subject.